Ratio of naturally retained 15N to 13C in rat brain regions as a marker of brain function and activity

Abstract

Our aim in the present study was to clarify the activity-dependent and function-associated retention of stable isotopes (SIs) in rat brain regions. We measured regional distributions of the natural stable isotopes 15N and 13C in brain using a mass spectrometer with a dual inlet system and a double collector for ratiometry, and compared them with distributions obtained from internal organs and skeletal muscle. Although levels of 15N and 13C were very high in brain regions of prenatal rats, and robustly decreased after birth, developmental changes in brain regions became obvious when the ratio of 15N to 13C (abbreviated as 15N/13C) in each brain region was compared. A high correlation was observed between free motor activity and 15N/13C in the hippocampus, cerebrum, and striatum. A significantly higher 15N/13C was also observed in the hippocampus and striatum of rats with higher intelligence, which was evaluated by radial maze learning. Furthermore, 15N/13C in brain regions of trained rats were significantly higher than those of untrained age-matched rats. Our study suggests that the 15N/13C in a specific brain region may reflect the physiological feature of the region. This ratio may hence be applicable as a maker for pathological research on undiagnosed brain diseases.